Scavenger receptor class B, type I (SR-BI) is a member of the CD36 superfamily. Each member contains a large extracellular domain flanked by two membrane-spanning domains with short amino and carboxy-terminal intracellular tails. CD36 family members maintain about 30% amino acid sequence identity. They can differ in subcellular localization and ligand preference. For example, CD36/SCARB3 is 29% identical to SR-BI and can bind HDL but is incapable of efficient uptake of HDL cholesterol via selective lipid uptake. There are several isoforms of SR-BI with the predominant one being isoform 1 (NP_058021). Isoform 2 (called SR-BII) differs by a 40 amino acid sequence in the C-terminus that is encoded by an alternative exon and has a reduced efficiency in selective uptake of HDL lipids.
SR-BI mediates selective uptake of cholesterol from high-density lipoprotein (HDL) particles through a poorly understood process that is dramatically different from classic cellular endocytic uptake of lipoproteins (e.g., the uptake of low-density lipoprotein (LDL) via LDL receptors). Among other things, SR-BI serves as a co-receptor for Hepatitis C Virus (HCV) viral entry. Thus, compounds that can interfere with the interaction of the HCV and SR-BI may block or reduce HCV infection. New tools are required to enhance our understanding of SR-BI function and mechanism of action, both in vitro and in vivo as well as new pharmaceutical agents for use in diseases or conditions involving the inhibition of SR-BI function, such as in the inhibition of pathogen (e.g., HCV) cell entry.